rs529579

Positions:

• chr19-34177389-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_015578.4(LSM14A):​c.121+4626T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.484 in 152,032 control chromosomes in the GnomAD database, including 18,636 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.48 (18636 hom., cov: 33)
• Consequence: LSM14A NM_015578.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.730

Genes affected

LSM14A (HGNC:24489): (LSM14A mRNA processing body assembly factor) Sm-like proteins were identified in a variety of organisms based on sequence homology with the Sm protein family (see SNRPD2; 601061). Sm-like proteins contain the Sm sequence motif, which consists of 2 regions separated by a linker of variable length that folds as a loop. The Sm-like proteins are thought to form a stable heteromer present in tri-snRNP particles, which are important for pre-mRNA splicing.[supplied by OMIM, Mar 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.56 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LSM14A	NM_015578.4	c.121+4626T>C		intron_variant		ENST00000544216.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LSM14A	ENST00000544216.8	c.121+4626T>C		intron_variant		1	NM_015578.4	P1

Frequencies

GnomAD3 genomes AF: 0.484 AC: 73544 AN: 151914 Hom.: 18628 Cov.: 33

Gnomad AFR AF: 0.438

Gnomad AMI AF: 0.722

Gnomad AMR AF: 0.389

Gnomad ASJ AF: 0.532

Gnomad EAS AF: 0.113

Gnomad SAS AF: 0.332

Gnomad FIN AF: 0.492

Gnomad MID AF: 0.573

Gnomad NFE AF: 0.565

Gnomad OTH AF: 0.502

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.484 AC: 73596 AN: 152032 Hom.: 18636 Cov.: 33 AF XY: 0.474 AC XY: 35239 AN XY: 74308

Gnomad4 AFR AF: 0.438

Gnomad4 AMR AF: 0.389

Gnomad4 ASJ AF: 0.532

Gnomad4 EAS AF: 0.113

Gnomad4 SAS AF: 0.333

Gnomad4 FIN AF: 0.492

Gnomad4 NFE AF: 0.565

Gnomad4 OTH AF: 0.498

Alfa AF: 0.516 Hom.: 4818

Bravo AF: 0.474

Asia WGS AF: 0.230 AC: 802 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.89
DANN	Benign	0.64

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs529579; hg19: chr19-34668294;